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LRRTM3 regulates activity-dependent synchronization of synapse properties in topographically connected hippocampal neural circuits

Title
LRRTM3 regulates activity-dependent synchronization of synapse properties in topographically connected hippocampal neural circuits
Author(s)
Kim, JinhuPark, DongseokSeo, Na-YoungYoon, Taek HanKim, Gyu HyunLee, Sang-HoonSeo, JinsooUm, Ji WonLee, Kea JooKo, Jaewon
DGIST Authors
Kim, JinhuPark, DongseokSeo, Na-YoungYoon, Taek HanKim, Gyu HyunLee, Sang-HoonSeo, JinsooUm, Ji WonLee, Kea JooKo, Jaewon
Issued Date
2022-01
Type
Article
Author Keywords
dentate gyrusexcitatory synapselong-term plasticityLRRTM3medial entorhinal cortex
Keywords
REPEAT TRANSMEMBRANE PROTEINSMOSSY FIBER-CA3 SYNAPSESDENTATE GYRUSMOLECULAR-MECHANISMSPLASTICITYSPECIFICITYNEUREXINMEMORYNEUROLIGINSINHIBITION
ISSN
0027-8424
Abstract
Synaptic cell-adhesion molecules (CAMs) organize the architecture and properties of neural circuits. However, whether synaptic CAMs are involved in activity-dependent remodeling of specific neural circuits is incompletely understood. Leucine-rich repeat transmembrane protein 3 (LRRTM3) is required for the excitatory synapse development of hippocampal dentate gyrus (DG) granule neurons. Here, we report that Lrrtm3-deficient mice exhibit selective reductions in excitatory synapse density and synaptic strength in projections involving the medial entorhinal cortex (MEC) and DG granule neurons, accompanied by increased neurotransmitter release and decreased excitability of granule neurons. LRRTM3 deletion significantly reduced excitatory synaptic innervation of hippocampal mossy fibers (Mf) of DG granule neurons onto thorny excrescences in hippocampal CA3 neurons. Moreover, LRRTM3 loss in DG neurons significantly decreased mossy fiber long-term potentiation (Mf-LTP). Remarkably, silencing MEC-DG circuits protected against the decrease in the excitatory synaptic inputs onto DG and CA3 neurons, excitability of DG granule neurons, and Mf-LTP in Lrrtm3-deficient mice. These results suggest that LRRTM3 may be a critical factor in activity-dependent synchronization of the topography of MEC-DG-CA3 excitatory synaptic connections. Collectively, our data propose that LRRTM3 shapes the target-specific structural and functional properties of specific hippocampal circuits. © This article is distributed under Creative Commons Attribution-NonCommercialNoDerivatives License 4.0 (CC BY-NC-ND).
URI
http://hdl.handle.net/20.500.11750/16123
DOI
10.1073/pnas.2110196119
Publisher
National Academy of Sciences
Related Researcher
  • 서진수 Seo, Jinsoo 뇌과학과
  • Research Interests iPSC; Alzheimer's disease; Neurodegeneration; Synapse; Neuroscience
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Appears in Collections:
Department of Brain Sciences Laboratory of Synapse Formation and Function 1. Journal Articles
Department of Brain Sciences Synapse Disorder Laboratory 1. Journal Articles
Department of Brain Sciences Laboratory of Aging Brain 1. Journal Articles

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